Polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA) are biodegradable polymers being extensively used for various biomedical applications especially as scaffold in the field of tissue engineering (Middleton J C, Tipton A J. Synthetic biodegradable polymers as orthopedic devices. Biomaterials 2000; 21: 2335-46; Papkov-Sokolsky M, Agashi K, Laya A, Shakesheff K, Domb A J. Polymer carrier for drug deliver and tissue engineering. Adv Drug Deliv Rev 2007; 59:187-206; Kohane D S, Langer R. Polymeric Biomaterials in Tissue Engineering. Pediatric Research 2008; 63: 487-91). Polymeric scaffolds serve as a physical support to provide cells with the appropriate three-dimensional architecture for in vitro cell culture as well as in vivo tissue regeneration (Langer R, Vacanti J P. Tissue Engineering. Science 1993; 260: 920-6; Griffith L G, Naughton G. Tissue engineering-current challenge and expanding opportunities. Science 2002; 295:1009-1014). Ideally, tissue engineering scaffolds formulated from biocompatible and bio-resorbable polymers like PLA should possess a well defined macrostructure and microstructure with controlled porous architecture to promote cell attachment and proliferation (Ma P X. Scaffold for tissue fabrication. Mater Today 2004; 7: 30-40; Nair L S, Laurencin C T. Polymers as biomaterials for tissue engineering and controlled drug delivery. Adv Biochem Eng/Biotechnol 2006; 102: 47-90; Chung H G and Park T G. Surface engineered and drug releasing pre-fabricated scaffolds for tissue engineering. Adv Drug Deliv Rev 2007; 59: 249-262). Apart from this, release of appropriate growth factors from the scaffold may promote controlled vascularization and tissue growth in three dimensions (Tabata Y. Significance of release technology in tissue engineering. Drug Discov Today 2005; 10: 1639-46; Biondi M, Ungaro F, Quaglia F, Netti P M. Controlled drug delivery in tissue engineering. Adv Drug Deliv Rev 2008; 60: 2229-42). Various methods like particulate leaching, emulsion freeze drying, phase inversion technique, solvent casting, electro spinning and thermal sintering have been employed to formulate scaffolds using PLA and PLGA for tissue engineering applications (Chung H G and Park T G. Surface engineered and drug releasing pre-fabricated scaffolds for tissue engineering. Adv Drug Deliv Rev 2007; 59: 249-262; Mikos A G et al. Preparation and characterization of poly (L-lactic acid) foams. Polymer 1994; 35: 1068-77; Hutmacher D W. Scaffold design and fabrication technologies for engineering tissues-state of the art and future perspectives. J Biomater Sci: Polym Ed 2001; 12: 107-24; Wu L, Jing D, Ding J. A “room-temperature” injection molding/particulate leaching approach for fabrication of biodegradable three-dimensional porous scaffolds. Biomaterials 2006; 27: 185-91; Ma P X. Biomimetic Materials for Tissue Engineering. Adv Drug Deliv Rev 2008; 60: 184-98; Shin M, Abukawa H, Troulis M J, Vacanti J P. Development of a biodegradable scaffold with interconnected pores by heat fusion and its application to bone tissue engineering. J Biomed Mater Res A 2008; 84(3): 702-9). PLA and PLGA nano fibers have also been used extensively as scaffold (Chen V J, Ma P X. Nano-fibrous poly (L-lactic acid) scaffolds with interconnected spherical macropores. Biomaterials 2004; 25: 2065-73; Liu X, Won Y, Ma P X. Porogen-induced surface modification of nano-fibrous poly(L-lactic acid) scaffolds for tissue engineering. Biomaterials 2006; 27: 3980-7; Guarino V, Causa F, Taddei P, Foggia M D, Ciapetti G, Martini D et al. Polylactic acid fibre-reinforced polycaprolactone scaffolds for bone tissue engineering. Biomaterials 2008; 29: 3662-70) and particularly for skin tissue engineering (Kumbar S G, Nukavarapu S P, James R, Nair L S, Laurencin C T. Electrospun poly (lactic acid-co-glycolic acid) scaffolds for skin tissue engineering. Biomaterials 2008; 29:4100-07; Zong X, Li S, Chen E, Garlick B, Kim K S, Fang D, et al. Prevention of post-surgery-induced abdominal adhesions by electrospun bioabsorbable nano-fibrous poly(lactide-co-glycolide)-based membranes. Ann Surg 2004; 240: 910-5) Particulate leaching method using different porogen is widely used to fabricate scaffolds but have problems of residual salts in the scaffold, irregularly shaped pores and poorly interconnected structures for three dimensional cell cultures (Mikos A G, Bao Y, Cima L G, Ingber D E, Vacanti J P, Langer R. Preparation of poly(glycolic acid) bonded fiber structures for cell attachment and transplantation. J Biomed Mater Res 1993; 27: 183-9). Wetting of polylactide particles or wafers transiently with an organic solvent like dichloromethane (DCM) to form scaffolds have also been tied (Mikos A G, Sarakinos G, Leite S M, Vacanti J P, Langer R. Laminated three-dimensional biodegradable foams for use in tissue engineering. Biomaterials 1993; 14: 323-30; Jaklenec A, Wan E, Murray M E, Mathiowitz E. Novel scaffolds fabricated from protein loaded microspheres for tissue engineering. Biomaterials. 2008; 29: 185-92). The disadvantage of such processes is that there is no control over the fusion process and prolonged exposure of polylactide particles to DCM results in loss of polymer particle characteristics. Labile biomolecules entrapped in the polymer scaffold also get denatured during interaction with organic solvent used for solubilization of the polymer.
Self-assembly is the organization of smaller units into regular three dimensional higher order structures without human intervention or involvement of external energy (Breen T L, Tien J, Oliver S R J, Hadzic T, Whitesides G M. Design and self-assembly of open, regular, 3D mesostructures. Science 1999; 284: 948-51; Whitesides G M, Grzybowski B. Self-assembly at all scales. Science 2002; 295: 2418-21; Capito R M, Azevedo H S, Velichko Y S, Mata A, Stupp S I. Self-Assembly of large and small molecules into hierarchically ordered sacs and membranes. Science 2008; 319: 1812-16). The classical example is the self-assembly of lipid molecules in nature into tubular microstructure (Schnur J M, Price R, Schoen P, Yager P, Calvert J M, Georger J, Singh A. Lipid-based tubule microstructures. Thin Solid Films 1987; 152: 181-206; Richard C, Balavoine F, Schultz P, Ebbesen T W, Mioskowski C. Supramolecular self-assembly of lipid derivatives on carbon nanotubes. Science 2003; 300: 775-78). Surfactant mediated self-assembly and synthesis of novel materials has been extensively investigated and utilized for various purposes including self assembly of nanoparticles in to higher order structure (Zemb Th, Dubois M, Demé B, Gulik-Krzywicki Th. Self-Assembly of flat nanodiscs in salt-free catanionic surfactant solutions. Science 1999; 283: 816-19; Inagaki S, Guan S, Ohsuna T, Terasaki O. An ordered mesoporous organosilica hybrid material with a crystal like wall structure. Nature 2002; 416: 304-07; Li M, Schnablegger H, Mann S. Coupled synthesis and self-assembly of nanoparticles to give structures with controlled organization. Nature 1993; 402: 393-95). Self-assembly of structures mediated by surfactant molecules tend to be mild, with little production of heat and friction and thus will be especially suited for bio-medical applications. Scaffold made from self assembling peptide nano fiber has been reported to accelerate wound healing (Hartgerink J D, Beniash E, Stupp S I. Peptide-amphiphile nanofibers: A versatile scaffold for the preparation of self-assembling materials. Proc Nat Acad Sci 2002; 99: 5133-8; Schneider A, Grlick J A, Egles C. Self-assembling peptide nanofiber scaffolds accelerate wound healing. Plos ONE 2008; 3: e1410). However the major limitations of self-assembly of molecules into scaffolds are their inability to control pore size, lack of stable morphology and biodegradability of the scaffold.